Cellular impedance biosensors for drug screening and toxin detection

Abstract

Cell-based impedance biosensing is an emerging technology that can be used to non-invasively and instantaneously detect and analyze cell responses to chemical and biological agents. This article highlights the fabrication and measurement technologies of cell impedance sensors, and their application in toxin detection and anti-cancer drug screening. We start with an introduction that describes the capability and advantages of cell-based sensors over conventional sensing technology, followed by a discussion of the influence of cell adhesion, spreading and viability during cell patterning on the subsequent impedance measurements and sensing applications. We then present an electronic circuit that models the cell-electrode system, by which the cellular changes can be detected in terms of impedance changes of the circuit. Finally, we discuss the current status on using cell impedance sensors for toxin detection and anti-cancer drug screening.

Figure 1

Design of a microelectrode array for cell impedance sensing: Gold-patterned substrate (left) and the material architecture of a single electrode (right).

Figure 2

(A) Schematic representation of a SAM-modified gold electrode coated with covalently-bound adhesion ligands for mediated cell adhesion. (B) Optical DIC image of a single 9L (rat glioma) cell adhered on the gold electrode coated with covalently-bound chlorotoxin ligand, revealing the well-spread cell morphology.

Figure 3

Illustration of current passing from an electrode through an adhered single cell that does not cover the entire electrode surface area (left) and one that fully spreads across the electrode (right). In the former, the current passes through the least resistive path between the electrode and electrolyte, resulting in cell signal loss.

Figure 4

Impedance model of a cell adhered to an electrode. Z₁ and Z₂ represent the basal and apical plasma membrane impedances, respectively, each with a resistive and a capacitive element in parallel. R_seal is the variable resistance between the cell and the substrate, increasing with the extent of cell spreading and focal adhesions. R_solution is the variable resistance of the electrolyte solution, determined by ion concentration in the solution. Z_E and Z_CE represent the characteristic impedances of the electrode and counter electrode and their interfacial impedance with the electrolyte solution. Z_CE is usually negligible in comparison to Z_E and Z_cell due to the large geometric size of counter electrode.